The aim of the present proposal is to test the hypothesis that the self-injurious behavior (SIB) shown by some children may reflect enhanced activity in some opioid peptide system(s) in the brain. The majority of Ss tested will have severe mental retardation, since SIB is a common problem in this population. Children were chosen as Ss since there may be an important developmental aspect to this phenomenon. The problems facing a child with SIB are significant including physical harm and a stunting a social and educational development. There is no recognized long-term treatment for SIB. The proposed investigation may reveal a component of the biochemical etiology of SIB and the pharmacological treatment of SIB in some children. Within a three year period, the major goal will be to investigate the effects of the potent opioid receptor antagonist - naltrexone - in the treatment of SIB in 12 severely self-injurious male children (3 to 18 years of age). A very conservative three phase test sequence will be used. The primary measure of drug effect will be decreases in the frequency of SIB in a structured test (The BRC Self-Injury Test). Phase I (10 weeks, single-blind) is an acute ascending dose-response series in which a single dose of placebo or naltrexone (0.5-, 1.0-, 1.5- and 2.0-mg/kg) is given once a week, and the S is tested on these days. Phase II (7 weeks, single- blind) is a chronic ascending dose-response series in which placebo or naltrexone (0.5-, 1.0-, 1.5- and 2.0-mg/kg) is given every other day three times a week, and S is tested on the third day of each week. Phase III (10 weeks) is a double-blind controlled trial in which Ss receive daily administration of placebo and 1.0 mg/kg of naltrexone each of three consecutive weeks (in an order unknown to S or investigators). A second goal will be to measure concentrations of the potent opioid peptide - B-endorphin - in the plasma of these 12 children and compare these data with those obtained from age- and sex-matched controls. The final aim will be to provide the first reference values for the ontogeny of immunoreactive B-endorphin in the plasma of 320 normal children (160 males, 160 females; 3 to 18 years of age) (160 samples have already been collected). Thus, the present proposal provides both pharmacological and biochemical tests of the Opioid Overactivity Self-Injury hypothesis.